Glycoprotein B Vaccine Is Capable of Boosting Both Antibody and CD4 T-Cell Responses to Cytomegalovirus in Chronically Infected Women

Sabbaj, Steffanie; Pass, Robert F.; Pichon, Sylvie; Goepfert, Paul

doi:10.1093/infdis/jir138

Cited by 102 publications

(79 citation statements)

References 33 publications

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“…Nevertheless, gB-specific CD4 + responses following gB/MF59 have been observed in seropositive recipients [70], but this has not been determined in seronegative recipients. It is likely that gB alone in the seronegative recipients does not promote a broad enough cellular immune response.…”

Section: Human Trials Of Subunit Gb Vaccinementioning

confidence: 95%

Section: Human Trials Of Subunit Gb Vaccinementioning

confidence: 99%

“…Studies have yet to establish the role of gB vaccination (and, therefore, antibody protection) in HCMV reactivation. However, one clinical study has highlighted that gB vaccination can generate a limited cellmediated immune response and is suggestive of an important role of CD4 + T cells in vertical HCMV transmission and potentially reinfection [70]. Interestingly, gB/MF59 boosted both the antibody-mediated and CD4…”

mentioning

confidence: 99%

“…They may even identify novel neutralizing epitopes that have not been found in prior studies. -Safety and immunogenicity HCMV-seronegative adolescent girls Safe, induces gB-specific antibodies and reduced probability of HCMV infections after two or three vaccine doses [70] HCMV: Human cytomegalovirus.The limited longevity of the immune responses generated by gB/MF59 vaccination also needs addressing. Studies in seronegative recipients have indicated that protective responses are not long lived [65], and a similar loss of boosted responses in seropositive recipients has been noted [68].…”

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confidence: 99%

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Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Manghera

McLean

2016

Future Virol.

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A vaccine for Human cytomegalovirus (HCMV) remains a high priority as complications following infection are observed in immunocompromised individuals and in congenitally infected neonates. Numerous preclinical and clinical studies have investigated vaccine strategies ranging from live attenuated preparations, nucleic acid-based approaches and recombinant delivery systems to subunit vaccines. These have defined the importance of both cell-mediated and humoral immunity to viral gB in the control of HCMV infection. This review will cover clinical trials investigating vaccine approaches that have incorporated gB and discuss the future perspectives of the recombinant gB subunit vaccine for HCMV. BackgroundHuman cytomegalovirus (HCMV) is a ubiquitous pathogen, known to infect all human populations worldwide [1]. It is an enveloped dsDNA virus that is the largest member of the Herpesviridae family that also includes important pathogens, such as HSV-1 and HSV-2, EBV and varicella zoster virus (VZV), all of which are widespread in human populations [2]. The HCMV genome is approximately 230 kbp encoding 200-250 open reading frames, many of which facilitate immune evasion [3]. A recent study of the HCMV genome and translation products has suggested that it may be even more complex than anticipated with regulation of alternate transcripts allowing for numerous polypeptides to be expressed [4]. Transmission of HCMV predominantly occurs via body fluids, such as saliva, blood, urine and breast milk, leading to contact of the mucosal surfaces, primarily infecting epithelial and endothelial cells, followed by dissemination to numerous organs and tissues [5]. HCMV is, therefore, able to infect a wide range of cells including endothelial cells, epithelial cells, fibroblasts, smooth muscle cells, leukocytes and dendritic cells [5,6]. Similarly to other Herpesviridae family members, HCMV is capable of both lytic and latent infections [7], but primary infection and reactivation from latency are often asymptomatic in immunocompetent individuals [8]. HCMV infection and reactivation in both solid organ and hematopoietic stem cell transplant recipients, and fetal exposure in utero poses a major threat. Immunocompromised individuals, including AIDS patients [9,10] and transplant patients [11,12], are at increased risk of both reactivation or reinfection, and primary HCMV infection has serious consequences for the developing fetus in pregnant women [8]. It is estimated that HCMV congenital infection occurs in 0.5-2% of all annual pregnancies [13], and approximately 10% of infants with congenital HCMV infection present with clinical manifestations at birth, such as hearing loss and neurological developmental defects [14]. Additionally, late-onset hearing disorders can occur with both symptomatic and asymptomatic congenital infection, which [17], which may also be effective in treating congenital infections [18]. Based on the widespread prevalence of HCMV, limited treatment options and the potential for significant morbidity, an effective ...

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Section: Human Trials Of Subunit Gb Vaccinementioning

confidence: 95%

Section: Human Trials Of Subunit Gb Vaccinementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Manghera

McLean

2016

Future Virol.

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“…However, the protection was not durable and it was predominantly observed within the first year after immunisation. Subsequent testing of gB-MF59 vaccine in seropositive women showed a significant boost in neutralising antibody titers and CD4 + T-cell responses 16 . Nevertheless, whether such boosting will provide protection against reactivation or reinfection with a different isolate in women with pre-existing immunity is not yet known.…”

Section: Subunit Vaccinesmentioning

confidence: 99%

Vaccination for cytomegalovirus: when, where and how

Dasari

Khanna

2015

Microbiol. Aust.

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Although following primary human cytomegalovirus (CMV)infection in many individuals no overt symptoms are observed, CMV came to medical attention due to its significant morbidity and mortality associated with congenital infec- In pregnant women following natural primary infection, viral replication is controlled by the emergence of antigen-specific CD4 + , CD8 + and CD45RA + effector memory T-cells 7,8 . Lower frequencies of CMV-specific CD4 + T-cells and CD45RA + cells in mothers following primary infection is known to be associated with virus transmission to the fetus 9,10 . Based on these observations it can be hypothesised that emergence of higher frequencies of CMV-specific CD4 + , CD8 + and CD45RA + effector memory T-cells may be associated with control of viremia and prevention of transplacental transmission. Therefore, an effective CMV vaccine specially designed to induce CMV-specific CD4 + , CD8 + and CD45RA + effector memory T-cells in women of reproductive age could potentially decrease CMV transmission to the fetus and vaccination of infants, toddlers and adolescents could reduce the duration of viral shedding, which may reduce child-to-mother transmission.Clinical evaluation of active and passive immunisation strategies against CMV in the context of congenital CMV Live attenuated virus vaccinesThe initial CMV vaccine trials based on an attenuated form of CMV isolates Towne and AD169 11,12 induced humoral and cellular Under the Microscope

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Cytomegalovirus infection in pregnancy

Davis

King

Kourtis

2017

Birth Defects Research

111

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Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. © 2017 Wiley Periodicals, Inc.

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Glycoprotein B Vaccine Is Capable of Boosting Both Antibody and CD4 T-Cell Responses to Cytomegalovirus in Chronically Infected Women

Cited by 102 publications

References 33 publications

Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Vaccination for cytomegalovirus: when, where and how

Cytomegalovirus infection in pregnancy

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